Early detection and screening is a key challenge in effectively treating peripheral arterial disease (PAD). Current diagnostic strategies are either to invasive, costly or not sensitive enough to be used for population- wide screening. Optical techniques have long been considered an option for this challenge due their cost- effective and noninvasive nature, and the fact that they are easily fit into current clinical paradigms. However, optical techniques have failed previously for a number of reasons including lack of quantitative accuracy. Recently, breakthroughs in wide-field optical imaging have enabled researchers to achieve higher degrees of quantitative accuracy, affording new potential for clinical deployment. The objective of this fellowship proposal is to develop and apply a novel in vivo noncontact, real-time optical imaging system capable of measuring oxygen metabolism called coherent spatial frequency domain imaging (cSFDI) imaging with the following aims: 1) Develop a system capable of measuring coregistered perfusion and chromophore concentrations in real- time. 2) Test real-time imaging of perfusion and chromophores on healthy subjects to characterize parameters related to metabolism. 3) Perform a small-scale clinical study using optical metabolic imaging on PAD patients undergoing exercise interventions. This project will exploit the ability of cSFDI to decouple in space and time multiple sources of contrast related to physiology. Specifically, cSFDI is capable of extracting 2 dimensional maps of structural details, while at the same time sequencing live samples fast enough to measure intrinsic physiology related to heartbeat, respirations, and the endothelial response to various challenges. Several features of this work make it well suited for the F30 mechanism. cSFDI, capable of measuring real- time metabolism, vascular function, perfusion, and structure in superficial tissues, was developed here by the trainee's sponsor Dr. Bruce Tromberg. Dr. Tromberg also serves as the director of the Beckman Laser Institute, a state-of-the-art imaging facility dedicated to new translational technologies related to biomedical optics. The proposed clinical measurements are done in collaboration with Dr. Shaista Malik, a cardiologist with an MD/PhD/MPH, at the UC Irvine Medical Center. Learning to integrate engineering concepts and breakthroughs into clinically translatable diagnostic platforms will help the trainee prepare for similar interdisciplinary work in his future research endeavors. Therefore, developing cSFDI as a clinical tool for PAD treatment monitoring will equip the trainee with technical imaging and data processing skills, in addition to improving his ability to perform clinical research.